Epidermal Growth Factor as a Biologic Switch in Hair Growth Cycle

Kingston K.L Mak,Siu Yuen Chan

doi:10.1074/jbc.m212082200

Abstract

The hair growth cycle consists of three stages known as the anagen (growing), catagen (involution), and telogen (resting) phases. This cyclical growth of hair is regulated by a diversity of growth factors. Although normal expression of both epidermal growth factor and its receptor (EGFR) in the outer root sheath is down-regulated with the completion of follicular growth, here we show that continuous expression of epidermal growth factor in hair follicles of transgenic mice arrested follicular development at the final stage of morphogenesis. Data from immunoprecipitation and immunoblotting showed that epidermal growth factor signals through EGFR/ErbB2 heterodimers in skin. Furthermore, topical application of tyrphostin AG1478 or AG825, specific inhibitors of EGFR and ErbB2, respectively, completely inhibited new hair growth in wild type mice but not in transgenic mice. When the transgenic mice were crossed with waved-2 mice, which possess a lower kinase activity of EGFR, the hair phenotype was rescued in the offspring. Taken together, these data suggest that EGFR signaling is indispensable for the initiation of hair growth. On the other hand, continuous expression of epidermal growth factor prevents entry into the catagen phase. We propose that epidermal growth factor functions as a biologic switch that is turned on and off in hair follicles at the beginning and end of the anagen phase of the hair cycle, guarding the entry to and exit from the anagen phase.

Highlights

The hair follicle is a regenerating system that undergoes cycles of renewal in three phases known as anagen, catagen, and telogen
This cyclical growth of hair is regulated by a diversity of growth factors. Normal expression of both epidermal growth factor and its receptor (EGFR) in the outer root sheath is down-regulated with the completion of follicular growth, here we show that continuous expression of epidermal growth factor in hair follicles of transgenic mice arrested follicular development at the final stage of morphogenesis
Transgenic mice demonstrated constitutive expression of EGF in the hair follicles (Fig. 1, f– h) which appeared to remain in stage 7– 8 of follicular morphogenesis according to published guidelines by Paus et al [28]

Summary

Epidermal Growth Factor as a Biologic Switch in Hair Growth Cycle*

Subcutaneous administration of EGF for 2 weeks into neonatal mice delayed the development of hair follicles and epidermis Both the growth of hair bulbs and hair fiber production were retarded. DNA synthesis in the matrix cells is inhibited, and they remain connected to the dermal papilla by a thin strand of epithelial cells, inducing an artificial catagen-like effect [5] Despite all these early studies, the physiological role of EGF on hair development and the signaling pathways involved remain unclear. Triple null mice lacking EGF, amphiregulin, and TGF-␣ demonstrate the same hair and skin phenotype as the TGF-␣ null mice [18] This suggests that other members of the EGF family can compensate for the loss of the three EGFR ligands.

EGF as Biologic Switch in Hair Growth Cycle

EXPERIMENTAL PROCEDURES

RESULTS

DISCUSSION